1. Field of the Invention
This invention pertains to a novel semi-enteric drug delivery systems which comprise an inert core, a first coating layer comprising a medicament, and a second coating layer comprising a mixture of methacrylic acid copolymer, type C, and povidone. Therapeutically effective amounts of the novel semi-enteric drug delivery systems may be utilized in a wide variety of pharmaceutically acceptable carriers and confectionery bulking agents to prepare medicated compositions. This invention also relates to methods for preparing and using these novel semi-enteric drug delivery systems and the medicated compositions in which they may be used.
2. Description of the Background
Enteric coated compositions for the delayed release of medicaments, the protection of acid-labile medicaments, or the encapsulation of irritating medicaments are well known in the art. Enteric coatings are applied to medicaments to prevent release and absorption until the medicament reaches the intestines. Enteric coating materials are generally anionic polymers which are insoluble in buffer solutions below about pH 5 and in gastric fluid but soluble in neutral to weakly alkaline buffer solutions above about pH 5.5 and in intestinal fluid. Release of the medicament within the enteric coating may occur by dissolution, leaching, erosion, rupture, diffusion, or similar actions, depending upon such factors as the nature and thickness of the coating material.
Because enteric coated compositions release no medicament in the stomach and rapidly release the medicament in the intestines, a frequently encountered problem is that such compositions provide only delayed release and not sustained release. This problem is particularly acute when constant blood levels of a medicament must be maintained such as when the medicament is an antibacterial.
U.S. Pat. No. 4,828,840, issued to Sakamoto, discloses a sustained release formulation which comprises an inert core, a powder-coating of an active ingredient, a powder-coating of a water-repellant ingredient, and a film-coating of a pH independent and water-insoluble material. The pH independent and water-insoluble film-coating material may be trimethylammoniummethyl chloride methacrylate (Eudragit.RTM. RS) or polyvinylpyrrolidone.
U.S. Pat. No. 4,263,273, issued to Appelgren et al., discloses an enteric pharmaceutical preparation which comprises an inert core, a first coating layer of a cardiac glycoside, and a second coating layer of an anionic carboxylic polymer insoluble below pH 7.5. The first layer may further comprise a water-soluble polymer such as polyvinylpyrrolidone and the anionic carboxylic polymer may be a partly methyl esterified methacrylic acid polymer such as Eudragit.RTM. L.
U.S. Pat. No. 4,800,079, issued to Boyer, discloses a pharmaceutical preparation which comprises an inert core, a first coating layer of fenofibrate incorporated into the pores of a matrix, and a second protective coating layer. The matrix and second protective coating layer are comprised of a material selected from a group which includes acid-soluble methacrylic acid polymer and polyvinylpyrrolidone.
U.S. Pat. No. 4,520,172, issued to Lehmann et al.. discloses an enteric emulsion polymer comprising (a) an alkyl acrylate or alkyl methacrylate, (b) a vinyl or vinylidene monomer having an amino or carboxylic group capable of salt formation, and (c) a vinyl or vinylidene monomer copolymerizable with the components in (a) or (b). The vinyl or vinylidene monomer may be vinylpyrrolidone. U.S. Pat. No. 4,644,031, issued to Lehmann et al., discloses an enteric pharmaceutical dosage form comprising an enteric polymer containing carboxylic groups and a water-insoluble film forming polymer. The enteric polymer and water-insoluble film forming polymer may be an acrylic acid and methacrylic acid copolymer which may also contain vinylpyrrolidone monomer. U.S. Pat. No. 4,705,695, issued to Lehmann et al., discloses an enteric coating comprising a polymer prepared from acrylic acid or methacrylic acid monomers containing a tertiary amine group. The enteric coating may also contain polyvinylpyrrolidone.
While the above references disclose a number of enteric coated compositions, none of the above references disclose semi-enteric compositions Enteric coated compositions provide only delayed release and do not provide sustained release. Thus it would be advantageous to prepare a semi-enteric drug delivery system which would partially release medicament in the stomach for immediate release and thereafter release additional medicament in the intestines for delayed release. The present invention provides such semi-enteric drug delivery systems which are useful to maintain constant blood levels of a medicament. The present invention also provides methods for preparing these novel semi-enteric drug delivery systems and the medicated compositions in which they may be used.